scholarly journals Numerical Chromosomal Abnormalities in Patients with Acute Lymphoblastic and Myeloid Leukemia in Iran

2012 ◽  
Vol 2 (5) ◽  
pp. 45-50
Author(s):  
Ali mohamad malekasgar ◽  
Mohamad Pedram ◽  
Sayyed kamal Eshagh housaini
Keyword(s):  
Myeloid Leukemia ◽  
Chromosomal Abnormalities

scholarly journals De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ismael F. Alarbeed ◽  
Abdulsamad Wafa ◽  
Faten Moassass ◽  
Bassel Al-Halabi ◽  
Walid Al-Achkar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Type A ◽  
Chemotherapeutic Treatment ◽  
Acute Myeloid ◽  
New Mutations

Abstract Background Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. Case presentation Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. Conclusions To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.

scholarly journals The possible significance of trisomy 8 in acute myeloid leukemia

2017 ◽  
Vol 5 (6) ◽  
pp. 2652 ◽  
Author(s):  
Salil N. Vaniawala ◽  
Monika V. Patel ◽  
Pratik D. Chavda ◽  
Shivangi H. Zaveri ◽  
Pankaj K. Gadhia
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chromosomal Aberrations ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Prognostic Significance ◽  
Chromosomal Translocation ◽  
Banding Technique ◽  
Trisomy 8 ◽  
Increased Risk ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while  three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.

scholarly journals S1614 CHROMOSOMAL ABNORMALITIES DETERMINE OUTCOME IN NPM1MUT/FLT3-ITDNEG/LOW ACUTE MYELOID LEUKEMIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 744-745
Author(s):  
L. Angenendt ◽  
C. Röllig ◽  
P. Montesinos ◽  
D. Martínez-Cuadrón ◽  
E. Barragan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Acute Myeloid

scholarly journals Deletion of PI3-Kinase Promotes Myelodysplasia Through Dysregulation of Autophagy in Hematopoietic Stem Cells

2020 ◽  
Author(s):  
Kristina Ames ◽  
Imit Kaur ◽  
Yang Shi ◽  
Meng Tong ◽  
Taneisha Sinclair ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Akt Pathway ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Phosphoinositide 3 Kinase

AbstractHematopoietic stem cells (HSCs) maintain the blood system through a delicate equilibrium between self-renewal and differentiation. Most hematopoietic growth factors and cytokines signal through phosphoinositide 3-kinase (PI3K) via three Class IA catalytic PI3K isoforms (P110α, β, and δ), encoded by Pik3ca, Pik3cb, and Pik3cd, respectively. The PI3K/AKT pathway is commonly activated in acute myeloid leukemia (AML), and PI3K is a common therapeutic target in cancer. However, it is not known whether PI3K is required for HSC differentiation or self-renewal. We previously demonstrated that individual PI3K isoforms are dispensable in HSCs1,2. To determine the redundant roles of PI3K isoforms in HSCs, we generated a triple knockout (TKO) mouse model with deletion of all three Class IA PI3K isoforms in the hematopoietic system. Surprisingly, we observed significant expansion of TKO HSCs after transplantation, with decreased differentiation capacity and impaired multilineage repopulation. Additionally, the bone marrow of TKO mice exhibited myelodysplastic features with chromosomal abnormalities. Interestingly, we found that macroautophagy (thereafter autophagy) is impaired in TKO HSCs, and that pharmacologic induction of autophagy improves their differentiation. Therefore, we have uncovered important roles for PI3K in autophagy regulation in HSCs to maintain the balance between self-renewal and differentiation.

scholarly journals Truncated RUNX1 Generated by the Fusion of RUNX1 to Antisense GRIK2 via a Cryptic Chromosome Translocation Enhances Sensitivity to Granulocyte Colony-Stimulating Factor

2020 ◽  
Vol 160 (5) ◽  
pp. 255-263 ◽  
Author(s):  
Akihiro Abe ◽  
Yukiya Yamamoto ◽  
Akira Katsumi ◽  
Hideyuki Yamamoto ◽  
Akinao Okamoto ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Chromosome Translocation ◽  
Leukemia Cells ◽  
Antisense Strand ◽  
Fusion Partner ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematological Disorders ◽  
Stimulating Factor

Fusions of the Runt-related transcription factor 1 (RUNX1) with different partner genes have been associated with various hematological disorders. Interestingly, the C-terminally truncated form of RUNX1 and RUNX1 fusion proteins are similarly considered important contributors to leukemogenesis. Here, we describe a 59-year-old male patient who was initially diagnosed with acute myeloid leukemia, inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). He achieved complete remission and negative CBFB-MYH11 status with daunorubicin/cytarabine combination chemotherapy but relapsed 3 years later. Cytogenetic analysis of relapsed leukemia cells revealed CBFB-MYH11 negativity and complex chromosomal abnormalities without inv(16)(p13;q22). RNA-seq identified the glutamate receptor, ionotropic, kinase 2 (GRIK2) gene on 6q16 as a novel fusion partner for RUNX1 in this case. Specifically, the fusion of RUNX1 to the GRIK2 antisense strand (RUNX1-GRIK2as) generated multiple missplicing transcripts. Because extremely low levels of wild-type GRIK2 were detected in leukemia cells, RUNX1-GRIK2as was thought to drive the pathogenesis associated with the RUNX1-GRIK2 fusion. The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. In summary, the RUNX1-GRIK2as fusion emphasizes the importance of aberrantly truncated RUNX1 in leukemogenesis.

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